During the past four years it has become apparent that all that is required to maintain the in vitro proliferation of activated T-lymphocytes, is the continual addition of a soluble proliferation trigger. This replication-inducing molecule, termed T-cell growth factor (TCGF), can directly influence the strength and duration of several cellular and humoral immune responses. Purification and iodination procedures have enabled the development of a highly sensitive radiolabeled TCGF binding assay. Such experimentation has revealed that only T-cell populations which proliferate in response to TCGF and absorb biologically active TCGF activity from cultures where it is present possess high affinity cell surface receptors for the growth factor. Resting T-cells lack receptors and without prior ligand stimulation will not proliferate in response to growth factor treatment. Therefore the degree of T-cell proliferation which serves to direct and mediate the outcome of many immune responses depends not only on the amount of TCGF produced, but presumably on the number of receptor-bearing effector cells generated and the affinity of these cell surface receptors. The research proposed in this application will apply these mechanistic principles of normal T-cell replication to the study of murine leukemia and lymphoma. Using techniques for monitoring TCGF production (TCGF microassay) and use (proliferation, absorption and binding of biologically active and radiolabeled TCGF) we will determine: (1) the TCGF production/use capacities of phenotypically selected subpopulations of normal and immature T-cells and (2) the kinetics and fate of TCGF receptor generation. To determine whether the unchecked replication of malignant T-cells is due to a breakdown in a particular aspect of TCGF-dependent proliferation control, multiple T-cell leukemia and lymphoma samples will be screened for TCGF production and use. Finally, we will attempt to develop a TCGF-specific radioimmonoassay capable of detecting physiologic concentrations (10 to the minus 9th power -10 to the minus 12th power M) of the growth factor. Armed with such an assay it will be possible to probe the in vivo significance of TCGF and determine in a controlled fashion whether TCGF methodologies have the capacity to influence and correct aberrant in vivo immune responses.